Center for Inherited Disease Research

1. Center for Inherited Disease Research CIDR Hello � Today I would like to explain how the Center for Inherited disease research can help your research project and how you get access to the Center. Hello � Today I would like to explain how the Center for Inherited disease research can help your research project and how you get access to the Center.

2. CIDR High-Throughput Genotyping Center for NIH Investigators NIH Contract to Johns Hopkins established in 1996 52 Staff Members Expertise in genotyping, statistical genetics, bioinformatics and project management CIDR is a high-throughput genotyping center. It�s funded through a Contract to Johns Hopkins University that was established by Francis Collins and Robert Nussbaum in 1996. There are 52 Staff Members, whose expertise includes the wet lab genotyping, statistical genetics, and bioinformatics. CIDR is a high-throughput genotyping center. It�s funded through a Contract to Johns Hopkins University that was established by Francis Collins and Robert Nussbaum in 1996. There are 52 Staff Members, whose expertise includes the wet lab genotyping, statistical genetics, and bioinformatics.

3. CIDR Services - GWAS Illumina Human660W-Quad Array Illumina Human1M-Duo Array Affymetrix SNP Array6.0 CIDR offers an array of genotyping resources that include both Affymetrix and Illumina genotyping for genome-wide association studies. The current 660W array is excellent for European derived populations, and includes considerable coverage of copy number variations. The Illumina 1M and Affymetrix SNP Array6.0 will cover a broad range of populations including African American populations. The arrays are changing and improving frequently. CIDR stays on top of the new array offerings and frequently are a beta testing laboratory for new arrays. CIDR offers an array of genotyping resources that include both Affymetrix and Illumina genotyping for genome-wide association studies. The current 660W array is excellent for European derived populations, and includes considerable coverage of copy number variations. The Illumina 1M and Affymetrix SNP Array6.0 will cover a broad range of populations including African American populations. The arrays are changing and improving frequently. CIDR stays on top of the new array offerings and frequently are a beta testing laboratory for new arrays.

4. CIDR Services Continued.. Illumina Human SNP Linkage panel Illumina Mouse Medium Density Linkage Custom Genotyping lllumina Cancer Panel Illumina MHC Panel In addition to the GWAS arrays, CIDR offers a number of other services. The have standard Linkage arrays for both Human and Mouse. They have custom gentoyping; the custom genotyping is most frequently used for follow up analysis after GWAS or Linkage studies. They also offer the Illumina Cancer and Major Histocompatibility Locus panels. In addition to the GWAS arrays, CIDR offers a number of other services. The have standard Linkage arrays for both Human and Mouse. They have custom gentoyping; the custom genotyping is most frequently used for follow up analysis after GWAS or Linkage studies. They also offer the Illumina Cancer and Major Histocompatibility Locus panels.

5. What CIDR Provides Investigators Full service � not just a wet lab run High quality genotyping CIDR genotyping is free to qualifying projects CIDR services are designed to maximize the chances of success from high-throughput genotyping. They provide full service � not just a wet lab run and the data that CIDR provides is of outstanding quality. Lastly, you can�t beat the price � It�s free to qualifying NIH investigators. CIDR services are designed to maximize the chances of success from high-throughput genotyping. They provide full service � not just a wet lab run and the data that CIDR provides is of outstanding quality. Lastly, you can�t beat the price � It�s free to qualifying NIH investigators.

6. Full Service Not Just a Wet Lab Run Dedicated Project Management SNP barcoding and sample performance pretesting Opportunity to replace samples Data cleaning So what do we mean by Full Service? 1) CIDR investigators are assigned to a project manager to walk them though all of the needed steps including sample plating etc. For example, for case-controls studies they maker sure that you know to have both cases and controls on each plate. When the samples go into the laboratory, they are run through a preliminary test that determines sample quality and provides a �barcode� to so that sample can be followed throughout each step. After pretesting, CIDR allows the investigator the opportunity to replace problematic samples at no additional cost. Lastly CIDR has careful data cleaning and SNP calling protcols to maximize data quality. So what do we mean by Full Service? 1) CIDR investigators are assigned to a project manager to walk them though all of the needed steps including sample plating etc. For example, for case-controls studies they maker sure that you know to have both cases and controls on each plate. When the samples go into the laboratory, they are run through a preliminary test that determines sample quality and provides a �barcode� to so that sample can be followed throughout each step. After pretesting, CIDR allows the investigator the opportunity to replace problematic samples at no additional cost. Lastly CIDR has careful data cleaning and SNP calling protcols to maximize data quality.

7. GWAS Overall Study Statistics I just want to show that CIDR has hard data to backup the claim of high data quality. In this slide we see the cumulative numbers for both Illumina and Affymetrix at CIDR. On the average 2% of the samples failed (requirements are somewhat higher for the Affymetrix arrays, therefore more replacements were required). Then the final genotyping results were extremely impressive. As you can see, the numbers are quite impressive for both services. For example, in the final genotyping runs, (that is after pretesting and replacement) 99% of Illumina samples are released with GWAS data. For those samples, 99.8% of the SNPs on the array are called, 99.8% of the SNPs provide good data. To get data of this quality requires a dedicated team � and as investigators who use CIDR will tell you, the CIDR team is really what makes everything work so well.I just want to show that CIDR has hard data to backup the claim of high data quality. In this slide we see the cumulative numbers for both Illumina and Affymetrix at CIDR. On the average 2% of the samples failed (requirements are somewhat higher for the Affymetrix arrays, therefore more replacements were required). Then the final genotyping results were extremely impressive. As you can see, the numbers are quite impressive for both services. For example, in the final genotyping runs, (that is after pretesting and replacement) 99% of Illumina samples are released with GWAS data. For those samples, 99.8% of the SNPs on the array are called, 99.8% of the SNPs provide good data. To get data of this quality requires a dedicated team � and as investigators who use CIDR will tell you, the CIDR team is really what makes everything work so well.

8. CIDR- The People I would just like to point out some of the senior staff: On the far right is Dave Valle who is a faculty member of Johns Hopkins and Director of CIDR. Kim Doheny is the Directory of the Laboratory and the person who oversees each step of the genotyping process. This is Corinne Boehm who leads the project management team and is usually the first person you have contact with when you gain CIDR access. Elizabeth Pugh is the Senior Statistical Geneticist leading the teams decision regarding such aspects as data cleaning and SNP calling. Mr Lee Watkins is the bioiformatics mavin who makes sure that the data pipline flows. I would just like to point out some of the senior staff: On the far right is Dave Valle who is a faculty member of Johns Hopkins and Director of CIDR. Kim Doheny is the Directory of the Laboratory and the person who oversees each step of the genotyping process. This is Corinne Boehm who leads the project management team and is usually the first person you have contact with when you gain CIDR access. Elizabeth Pugh is the Senior Statistical Geneticist leading the teams decision regarding such aspects as data cleaning and SNP calling. Mr Lee Watkins is the bioiformatics mavin who makes sure that the data pipline flows.

9. Getting Access to Free Genotyping at CIDR Support of CIDR Member NIH Institute 2) CIDR Access Committee Approval Via Peer Review Process So, how do you get access to CIDR, and free genotyping? First, you must be supported by an NIH institute that is a member of CIDR, next you must gain CIDR Access Committee Approval. So, how do you get access to CIDR, and free genotyping? First, you must be supported by an NIH institute that is a member of CIDR, next you must gain CIDR Access Committee Approval.

10. Institute Approval NCI Liaison to CIDR Daniela Seminara seminard@mail.nih.gov Fortunately, NCI is a member of CIDR. If you would like to apply for CIDR access you will need the approval Dr. Daniela Semina, who is the NCI liaison to CIDR. It is recommended that you contact her 2 months before the application due date. Fortunately, NCI is a member of CIDR. If you would like to apply for CIDR access you will need the approval Dr. Daniela Semina, who is the NCI liaison to CIDR. It is recommended that you contact her 2 months before the application due date.

11. CIDR Access Committee Approval Applications are submitted as an X01 program announcement: PAR-08-258 Submission Dates are the first weekday in March, July and November. To get CIDR Access Committee approval, you�ll submit an application via our program announcement (PAR-08-258). The application submission dates are the beginning of March, July and September. To get CIDR Access Committee approval, you�ll submit an application via our program announcement (PAR-08-258). The application submission dates are the beginning of March, July and September.

12. Considerations for Access Evidence for a detectable genetic component Complexity of the trait under study and the need for a high-throughput genotyping Quality and completeness of phenotypic measures The CIDR Access committee doesn�t review your R01, they look specifically at criteria designed to determine your likelihood that the project will result in important new information about genetic variants important in human health or disease The CIDR Access committee doesn�t review your R01, they look specifically at criteria designed to determine your likelihood that the project will result in important new information about genetic variants important in human health or disease

13. Considerations for Access Con.. Appropriateness of the study design Power of the sample set to detect a genetic effect Plans for data analysis and data management Expertise of the team Plans for follow-up studies Similarly they are looking at whether the study design will maximizes your chances of finding genetic elements. Is the power sufficient? (That should be documented in the application.) They will also been looking at the data management and the teams ability to handle this part of the project. For example, for GWAS projects it�s expected that there will be an experienced genetic analyst who is a major collabortor with dedicated time to spend on that activity. That person should be involved upfront with your study design and your CIDR application. Although not a major aspect of the application, reviewers look at your plans for follow up studies as a further indication of the likelihood of success. Similarly they are looking at whether the study design will maximizes your chances of finding genetic elements. Is the power sufficient? (That should be documented in the application.) They will also been looking at the data management and the teams ability to handle this part of the project. For example, for GWAS projects it�s expected that there will be an experienced genetic analyst who is a major collabortor with dedicated time to spend on that activity. That person should be involved upfront with your study design and your CIDR application. Although not a major aspect of the application, reviewers look at your plans for follow up studies as a further indication of the likelihood of success.

14. CIDR Access Committee Bernie Devlin (Chair); Goncalo Abecasis; Laura Almasy; Nancy Cox; Lynn Jorde; Suzanne Leal; Douglas Levinson; Deborah Meyers; Gloria Petersen; Duncan Thomas; Jeffery Vance; John Witte Here is our current committee. Some members retire each summer and new members start generally with the September review. All CIDR reviewers are senior geneticists, statistical genetics and genetic epidemiologists. This is our current committee, some reviewers rotate off each summer and new member come on usually at the September review. Here is our current committee. Some members retire each summer and new members start generally with the September review. All CIDR reviewers are senior geneticists, statistical genetics and genetic epidemiologists. This is our current committee, some reviewers rotate off each summer and new member come on usually at the September review.

15. Summary CIDR is a high-throughput genotyping center that can generate high quality data for genetic studies CIDR genotyping is free to qualifying investigators CIDR is accessed through a peer review process For more information: http://www.cidr.jhmi.edu/ camilla.day@nih.gov